Mesenchymal stem cells (MSCs) are pluripotent blast or embryonic-like cells located in blood, bone marrow, dermis and periosteum. In general these cells are capable of renewing themselves over extended periods of time as well as, under various environmental conditions, differentiating into cartilage, bone and other connective tissue. Recently, various investigators have researched the potential for using these cells to repair or regenerate target tissues, e.g., bone, cartilage, cardiac muscle, etc. In this manner MSCs have been reported to have regenerative capabilities in a number of animal models. See Acosta et al. (2005) Neurosurg Focus 19(3):E4; Barry (2003) Novartis Found Symp. 249:86-102, 170-4, 239-41; Brisby et al. (2004) Orthop Clin. North Am. 35(1):85-89; Buckwalter and Mankin (1998) Instr Course Lect. 47:487-504; Caplan (1991) J Orthop Res. 9(5):641-650.
Recent research has shown that tissue injury can act as a homing signal for bone marrow derived MSCs to migrate to the site of injury. (Agung et al., Knee Surg. Sports Traumatol Arthrosc, 2006, 14(12):1307-14). However, these studies utilized a surgical approach to include a gross tissue injury which was shown to signal MSCs to the injury site, this approach is, however, likely impractical for clinical care (for example cutting portions of an ACL ligament to signal MSC homing to the ACL site could result in more damage than actual repair to the ACL). Note also that other researchers have discussed the possibility that tissue injury can act as a homing signal for MSCs into various tissues. (Ramirez et al., Br J Sports Med., 2006 40(8):719-22; Shyu et al., Front Biosci., 2006 11:899-907).
In addition, injectable hyperosmolar substances that initiate tissue injury and potentially prompt healing in a clinical setting have been utilized to varying success. (Centeno et al., Pain Physician, 2005, 8(1):67-72; Mooney, V., Spine J, 2003 3(4):253-4; Reeves et al., J Altern Complement Med., 2000 6(4):311-20; and Reeves et al., Altern Ther Health Med 2000 6(2):68-74). However, these procedures have had limited practical success in the health care setting.
Clinical advantage could be gained through minimally invasive medical procedures that impart stem cells to a site of need within a patient (for example, percutaneous injection of MSCs to a site in need). Unfortunately, mere implantation of stem cells to a site in this manner has proven mostly ineffective. As such, there is a need in the health care setting to more optimally utilize stem cell implants as well as to facilitate repair of sites in a patient without first grossly injuring the site to initiate a repair process.
Against this backdrop the present invention was developed.